WO2021049898A1 - System for corneal cross-linking and correcting vision by using led contact lens and eye dye - Google Patents

System for corneal cross-linking and correcting vision by using led contact lens and eye dye Download PDF

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Publication number
WO2021049898A1
WO2021049898A1 PCT/KR2020/012280 KR2020012280W WO2021049898A1 WO 2021049898 A1 WO2021049898 A1 WO 2021049898A1 KR 2020012280 W KR2020012280 W KR 2020012280W WO 2021049898 A1 WO2021049898 A1 WO 2021049898A1
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Prior art keywords
cornea
hyaluronic acid
contact lens
vision correction
dye
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PCT/KR2020/012280
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French (fr)
Korean (ko)
Inventor
한세광
신상배
문종환
Original Assignee
주식회사 화이바이오메드
포항공과대학교 산학협력단
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Priority claimed from KR1020200044528A external-priority patent/KR102402136B1/en
Application filed by 주식회사 화이바이오메드, 포항공과대학교 산학협력단 filed Critical 주식회사 화이바이오메드
Priority to US17/642,565 priority Critical patent/US20220323780A1/en
Publication of WO2021049898A1 publication Critical patent/WO2021049898A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A61F9/007—Methods or devices for eye surgery
    • A61F9/0079—Methods or devices for eye surgery using non-laser electromagnetic radiation, e.g. non-coherent light or microwaves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • G—PHYSICS
    • G02—OPTICS
    • G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
    • G02C11/00—Non-optical adjuncts; Attachment thereof
    • G02C11/04—Illuminating means
    • G—PHYSICS
    • G02—OPTICS
    • G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
    • G02C7/00—Optical parts
    • G02C7/02—Lenses; Lens systems ; Methods of designing lenses
    • G02C7/04—Contact lenses for the eyes
    • G—PHYSICS
    • G02—OPTICS
    • G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
    • G02C7/00—Optical parts
    • G02C7/02—Lenses; Lens systems ; Methods of designing lenses
    • G02C7/04—Contact lenses for the eyes
    • G02C7/049—Contact lenses having special fitting or structural features achieved by special materials or material structures
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
    • A61N2005/0643—Applicators, probes irradiating specific body areas in close proximity
    • A61N2005/0645—Applicators worn by the patient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/065—Light sources therefor
    • A61N2005/0651—Diodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
    • A61N2005/0662—Visible light
    • A61N2005/0663—Coloured light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent

Definitions

  • the present invention relates to a corneal bonding and vision correction system using an LED contact lens and an eye dye.
  • Conical cornea is an eye disease caused by protruding as the thickness of the cornea becomes thin and has a great effect on vision.
  • the causes include genetic factors, excessive irritation and exposure to ultraviolet rays, and symptoms such as decreased contrast, decreased vision, negative astigmatism, glare, and distortion.
  • Methods of treating this include methods of using instruments such as wearing orthodontic glasses and corrective contact lenses, and surgery such as corneal transplantation and intracorneal ring insertion.
  • Patent Document 1 a hard lens for conical cornea treatment must be worn.
  • the hard lens has a flat central portion, and when the lens is worn, the wearer's corneal portion is temporarily deformed, so that vision can be corrected.
  • vision correction for myopia and irregular astigmatism is possible.
  • As a surgical method there is a method of reducing irregular astigmatism by inserting a semicircular ring in the corneal parenchyma, or a method of exposing the corneal surface to perform a procedure.
  • the surgical method may make the patient feel a foreign body or give a feeling of rejection to surgery to expose the cornea.
  • the conical cornea can be effectively and safely treated, and new treatments and procedures are required without the burden of regular wear or surgery to the patient.
  • An object of the present invention is to provide a corneal bonding and vision correction system using an LED contact lens and an eye dye.
  • the present invention hyaluronic acid-dye conjugate
  • It provides a system for bonding damaged cornea, conical cornea treatment, or vision correction including a contact lens including an LED light source.
  • the present invention also includes the steps of applying a hyaluronic acid-dye conjugate to the cornea of a subject;
  • It provides a method for bonding damaged cornea, conical cornea treatment, or vision correction using the above-described damaged cornea bonding, conical cornea treatment, or vision correction system, including the step of irradiating light from an LED light source in a contact lens to the cornea of a target.
  • the present invention hyaluronic acid-dye conjugate; And it provides a system for bonding damaged cornea, conical cornea treatment or vision correction comprising a contact lens including an LED light source.
  • the dye is activated by receiving light irradiated from the LED light source of the contact lens to generate radicals, thereby generating covalent bonds between amino acid radicals between corneal collagen, and strengthening the collagen layer.
  • the hyaluronic acid-dye conjugate in which hyaluronic acid is bonded to the dye may be used to improve the permeability of the dye to the cornea, and the permeability of the dye may be further improved by using a contact lens together.
  • the contact lens since the contact lens has a structure that presses the center of the cornea, it can have a vision correction effect by changing the shape of the cornea.
  • the system according to the present invention can be used to treat damaged cornea junctions, conical corneas, cornea injuries, and the like, and can be used for a wide range of vision correction.
  • FIG. 4 shows the results of analyzing the thickness of the cornea through an image in which the cornea is stained through H&E.
  • 6a and b show the fabrication of an ASIC device, and show computer simulation, layout, and final inspection results.
  • FIG. 7 shows an example of a custom semiconductor and electronic device configured on a plastic substrate.
  • the present invention hyaluronic acid-dye conjugate
  • It relates to a system for bonding damaged cornea, conical cornea treatment or vision correction, including a contact lens including an LED light source.
  • collagen conjugation (can be referred to as corneal collagen cross-linking, corneal collagen cross-linking, or Corneal Collagen Cross-linking) is a treatment method designed so that the eyeball is no longer pushed forward by strengthening the weakened cornea.
  • the cornea is made up of collagen.
  • Collagen structures have a structure that is not separated but interlocked with each other. If the bonding strength of the structures is not strong, the cornea cannot maintain its original shape and is deformed.
  • the conical cornea has a state in which this bonding force is less than normal. Therefore, it is possible to treat the conical cornea by increasing the binding power of collagen.
  • the collagen conjugation procedure is performed by infiltrating a dye into the cornea and then applying ultraviolet rays thereon. That is, in collagen bonding, corneal bonding may be achieved by crosslinking of corneal collagen.
  • crosslinking refers to the formation of chemical links between molecular chains in collagen fibers.
  • corner junction means that corneal collagen forms crosslinks.
  • the cross-linking of the corneal collagen can increase the mechanical properties of the weakened cornea, and can treat the conical cornea in which the cornea becomes thinner. In addition, it is possible to have a vision correction effect through the collagen conjugation.
  • Damaged cornea conjugation, conical cornea treatment or vision correction system according to the present invention is hyaluronic acid-dye conjugate; And a contact lens including an LED light source.
  • the hyaluronic acid-dye conjugate is a compound in which hyaluronic acid and a dye are chemically combined.
  • hyaluronic acid not only has biocompatibility and biodegradability, but also has transdermal delivery properties, so it can be safely applied to the human body, and can be applied to a transdermal drug delivery system of various protein drugs and chemical drugs including antigenic proteins. It has an advantage.
  • HA Hyaluronic acid
  • HA refers to a polymer having a repeating unit represented by the following general formula 1, and includes all salts or derivatives of hyaluronic acid. Is used.
  • n may be an integer of 25 to 10,000.
  • the'hyaluronic acid derivative' is an amine group, an aldehyde group, a vinyl group, a thiol group, an allyloxy group, N-succinimidyl-3-(2-pyridyl) based on the basic structure of hyaluronic acid in the general formula 1 above.
  • All variants of hyaluronic acid in which functional groups such as dildithio) propionate (N-Succinimidyl-3-(2-pyridyldithio)propionate, SPDP) and N-hydroxysuccinimide (NHS) are introduced Refers to.
  • HA-diaminobutane HA-hexamethylenediamine
  • HA-aldehyde HA-adipic acid dihydrazide
  • HA-Adipic Acid Dihydrazide HA-ADH
  • HA-2-Aminoethyl methacrylate hydrochloride HA-Spermine
  • HA-spermidine HA- spermidine
  • HA-SPDP or HA-NHS.
  • the hyaluronic acid is present in most animals and can be safely applied to the human body as a linear polysaccharide polymer without biodegradability, biocompatibility, or immune response.
  • Hyaluronic acid can be used for various purposes because it plays a number of different roles depending on the molecular weight in the body.
  • Hyaluronic acid, a salt of hyaluronic acid, or a derivative of hyaluronic acid used in the present invention is not limited in its composition, but may preferably have a molecular weight of 10,000 to 3,000,000 Daltons (Da).
  • Hyaluronic acid, or a salt of hyaluronic acid, or a derivative of hyaluronic acid having a molecular weight in the above range is suitable for use in conjugates for drug delivery.
  • the dye generates a radical by the light irradiated from the LED light source of the contact lens to be described later, through which corneal bonding can be achieved.
  • the type of the dye is not particularly limited, and an eye dye may be used.
  • an eye dye may be used.
  • the eye dyes rosebangal, riboflavin, ethyl eosin, eosin Y, fluorescein, 2,2-dimethoxy, 2-phenylacetophenone, 2-methoxy, 2-phenylacetophenono, camphorquinone, One or more selected from the group consisting of methylene blue, erythrosine, phloxime, thionine and methylene green may be used.
  • rose bangal or riboflavin may be used as a dye.
  • the riboflavin is activated when receiving light with a wavelength of 354 nm and rose bangal with a wavelength of 532 nm, thereby forming a radical, thereby creating a covalent bond between amino acid radicals between the corneal collagen to form a collagen layer.
  • the hyaluronic acid-dye conjugate is a conjugate in which a carboxyl group of hyaluronic acid and a carboxyl group of a dye are bonded through a linker.
  • a diamine compound may be used as the linker, and the diamine compound is a group consisting of diaminohexane (hexamethylenediamine), ethylenediamine, butylenediamine, pentaethylenehexaamine, and 1,5-diamino-2-methylpentane It may be one or more selected from.
  • diaminohexane hexamethylenediamine
  • ethylenediamine ethylenediamine
  • butylenediamine pentaethylenehexaamine
  • 1,5-diamino-2-methylpentane It may be one or more selected from.
  • a hyaluronic acid-dye conjugate in which a dye and hyaluronic acid are bound may be used to improve the permeability of the dye to the cornea.
  • the contact lens is an elastomer of a silicone elastomer; Silicone hydrogel; Polydimethyloxane (PDMS); Poly(2-hydroxyethylmethacrylate) (PHEMA); And polyethylene glycol methacrylate (poly(ethylene glycol) methacrylate, PEGMA); It may be based on one or more polymers selected from the group consisting of.
  • the contact lens may be a contact lens that is conventionally used for vision correction, which incorporates an LED light source, or may be manufactured and used in a laboratory or the like.
  • the contact lens has a structure having a flat surface, specifically, a central portion, and accordingly, when the lens is worn, the corneal portion of the wearer (target) is temporarily deformed to correct visual acuity.
  • the contact lens includes an LED light source.
  • a light source to a contact lens, it is possible to stably irradiate light to the cornea of a target.
  • the LED light source may be a micro LED (MicroLED, mLED, ⁇ LED).
  • the LED light source that is, the micro LED, may be a product generally used in the art, or may be directly manufactured and used.
  • the LED light source may irradiate light onto the cornea.
  • the dye may receive the light to generate radicals, thereby performing corneal collagen conjugation.
  • the LED light source may be configured by selecting LEDs emitting light of a specific wavelength according to the purpose of use. For example, the LED light source may irradiate light having a wavelength of 350 to 550 nm, 350 to 380 nm, or 520 to 550 nm.
  • the position of the LED light source in the contact lens is not particularly limited, and the position can be appropriately adjusted.
  • a transparent substrate may be formed inside the contact lens, and the LED light source may be formed on the transparent substrate.
  • the transparent substrate may have excellent light transmittance, flexibility, and elasticity. In addition, the transparent substrate has excellent biocompatibility characteristics.
  • the transparent substrate may include at least one selected from the group consisting of Parylene C, PDMS, silicone elastomer, polyethylene terephthalate (PET), and polyimide (PI).
  • the LED light source may be formed on the surface in the direction of the eyeball on the transparent substrate.
  • the contact lens of the present invention may further include at least one selected from the group consisting of an application specific integrated circuit (ASIC), a battery, and an antenna.
  • ASIC application specific integrated circuit
  • the application specific semiconductor device may be used for wireless control and power transmission of an LED light source.
  • These customized semiconductors include 1. Digital control, 2. Relaxation oscillator, 3. Carrier frequency generator, 4. Bandgap reference generator, 5. Vdd generator ( Vdd generator).
  • the custom semiconductor can be manufactured and used according to the intended use.
  • the battery may be a rechargeable, flexible thin-film battery.
  • the thin-film battery it is possible to wirelessly drive a contact lens, and a system capable of operating without supplying power from the outside may be implemented.
  • the battery may supply power to elements constituting the contact lens.
  • the thin-film battery may be a product used in the art, and may be directly manufactured and used.
  • the antenna may transmit and receive power and signals to the outside through induced current and electromagnetic resonance.
  • the antenna may be a circular antenna having a circular structure.
  • the antenna may be made of a nanomaterial, and the nanomaterial may include a metal thin film material; 0-dimensional material that is a nanoparticle; One-dimensional nanomaterials such as nanowires, nanofibers, or nanotubes; And graphene, MoS 2 or may include one or more selected from the group consisting of two-dimensional nanomaterials that are nanoflakes.
  • the antenna may include a silver nanowire or a silver-gold core-shell nanowire (Ag@Au core-shell NW).
  • the antenna may be composed of a wireless electric antenna for receiving externally generated power, that is, wireless power, and a radio frequency antenna for data communication.
  • the role of the battery can be supplemented by using a wireless electric antenna.
  • the wireless electric antenna may receive power generated from a wireless electric coil of smart glasses, which will be described later.
  • the received power can be used for driving an LED light source through control of an on-demand semiconductor device.
  • the above-described customized semiconductor device, battery, and antenna may be formed on a transparent substrate to facilitate manufacturing and driving.
  • the custom semiconductor device, the battery, and the antenna may be formed on the transparent substrate in the direction of the eyeball, that is, on the same surface as the LED light source.
  • the contact lens including the LED light source comprises the steps of (S1) forming a sacrificial layer dissolved in water on a handling substrate;
  • (S4) It may be manufactured through the step of transferring the transparent substrate on which the LED light source is formed into a contact lens.
  • Step (S1) is a step of forming a sacrificial layer on a handling substrate.
  • the sacrificial layer may serve as an adhesive layer between the handling substrate and the transparent substrate, and may help transfer the transparent substrate on which the LED light source is formed.
  • This sacrificial layer is not particularly limited as long as it can be dissolved in water, and may include at least one selected from the group consisting of polyvinyl alcohol (PVA) and dextran (DEXTRAN).
  • Step (S2) is a step of forming a transparent substrate on the sacrificial layer, the sacrificial layer serves as an adhesive. Accordingly, the transparent substrate can be easily attached to the handling substrate, and can be easily separated from the handling substrate through the dissolution of the sacrificial layer in a later process.
  • the transparent substrate may be made of a material having excellent light transmittance, and the above-described type may be used.
  • Step (S3) is a step of forming an LED light source on a transparent substrate.
  • the LED light source may be bonded to the transparent substrate using a human body compatible epoxy, for example, Ag epoxy.
  • step (S4) is a step of transferring the transparent substrate on which the LED light source is formed into the contact lens.
  • the LED light source fabricated on the sacrificial layer can be transferred while melting the sacrificial layer in biocompatible water.
  • the present invention may further include forming an on-demand semiconductor device, a battery, and an antenna on a transparent substrate. This step may be performed when performing step (S3).
  • the on-demand semiconductor device includes depositing a metal such as gold or aluminum on a transparent substrate, and then forming a metal pad through an etching method using a photolithography process; And
  • It may be manufactured by bonding the device to the metal pad through a flip-chip bonding process.
  • the device may be bonded through an ultrasonic and thermal compression process using a non-conductive adhesive.
  • the battery may be formed on the transparent substrate in the same manner as the LED light source.
  • the antenna comprises the steps of: (a1) forming a mask material for patterning on a transparent substrate;
  • (a3) It may be manufactured through the step of forming a passivation layer on the patterned sensor and circuit.
  • Step (a1) is a step of forming a mask material for patterning on a transparent substrate.
  • the mask material may serve as a shadow mask, and the nanomaterial may be patterned through the use of the mask material.
  • a material that can be used as a photoresist may be used, and specifically, LOF, AZ series, and the like may be used.
  • Step (a2) is a step of patterning a sensor and a circuit by coating a nanomaterial on a transparent substrate on which a mask material is formed through a lift-off process.
  • a pattern of nanomaterials may be formed.
  • the above-described types may be used, and specifically, silver nanowires or silver-gold core-shell nanowires (Ag@Au core-shell NW) may be used.
  • the nanomaterial prepared in the above step may function as an antenna.
  • the circuit manufactured in the above step may serve to connect an LED light source, a semiconductor device, an antenna, and a battery.
  • Step (a3) is a step of forming a passivation layer on the patterned antenna and circuit.
  • system of the present invention may further include smart glasses.
  • the smart glasses may control driving of the LED light source of the contact lens by transmitting or receiving an electrical signal wirelessly.
  • the driving power of the smart glasses may use a rechargeable lithium-ion battery, and wireless communication with a smart device may be performed using a bluetooth module in the smart glasses.
  • the smart glasses may be paired with a smartphone, a smart watch, or a PC.
  • the built-in lithium ion battery can be used for power, and a photocell can be inserted for self-powering.
  • the total weight of the smart glasses is less than 20g, and Wi-Fi 802.11b/g, Bluetooth, and micro USB may be possible.
  • the system according to the invention can be used for the bonding of damaged corneas and for the treatment of conical corneas. It can also be used for vision correction.
  • the present invention relates to a method for conical cornea bonding, conical cornea treatment, or vision correction using the above-described damaged cornea bonding, conical cornea treatment or vision correction system.
  • the method according to the present invention comprises the steps of (A) applying a hyaluronic acid-dye conjugate to the cornea of a subject;
  • Step (A) is a step of applying a hyaluronic acid-dye conjugate to the cornea of a subject.
  • the hyaluronic acid-dye conjugate is prepared in the form of an eye drop, which is a liquid composition, and can be applied to the cornea by dropping (loading) it onto the cornea.
  • the dye can be applied to the cornea without surgery to remove the surface layer of the cornea by binding hyaluronic acid to the eye dye.
  • the conjugate penetrates the surface layer of the cornea and can be successfully delivered to the corneal stroma where a large amount of collagen is distributed, and thus, can have high permeability to the cornea.
  • Step (B) is a step of wearing a contact lens including an LED light source.
  • the contact lens including the LED light source according to the present invention may have the same structure as a conventional lens for vision correction, and specifically, a central portion may be flat. Through this, when the lens is worn, it becomes a structure that presses the center of the cornea, thereby deforming the shape of the cornea, which is effective in correcting vision.
  • the hyaluronic acid-dye conjugate is loaded on the corneal surface and the contact lens is worn, the hyaluronic acid-dye can be better transmitted to the corneal parenchyma due to the wearing pressure.
  • Step (C) is a step of irradiating light from the LED light source in the contact lens to the cornea of the target.
  • the dye is activated by receiving light irradiated from the LED light source of the contact lens to generate radicals, thereby generating covalent bonds between amino acid radicals between corneal collagen, and strengthening the collagen layer.
  • the wavelength of light irradiated from the LED light source may be 350 to 550 nm, 350 to 380 nm, or 520 to 550 nm.
  • the irradiation time may vary depending on the amount of light, and may be, for example, 200 to 800 seconds.
  • the method of the present invention may additionally use smart glasses.
  • the wireless power which is the power generated from the wireless electric coil of the smart glasses, is received from the wireless electric antenna of the contact lens, and the power received through the control of the customized semiconductor element can be used to drive the LED light source.
  • the above graph of FIG. 1 shows the absorbance of the hyaluronic acid-rose bengal conjugate, and it can be seen that the rose bengal's own pick has been substituted from 540 nm to 580 nm.
  • the graph below of FIG. 1 shows the results of FT-IR analysis of pure rose bangal (left) and hyaluronic acid-rose bangal conjugate (right), showing that a pick that is not observed in pure rose bangal is observed near 3000 nm. I can confirm. Through this, it can be confirmed that the hyaluronic acid-rosebangal conjugate was successfully synthesized.
  • Example 2 The hyaluronic acid-rosebangal conjugate synthesized in Example 1 was dropped on the bovine ocular cornea at 5 minute intervals for 30 minutes. As a control group, a pure rose-bangal solution was dropped in the same way.
  • the cornea was removed from the bovine eye to perform a two-photon image analysis.
  • HA-RB hyaluronic acid-rose bengal conjugate
  • the pressure inside the bovine eye was measured through a tonometer. Then, the hyaluronic acid-rose bengal conjugate solution and the rose bengal solution were respectively dropped on the affected area in which the wound was induced, and the 532 nm laser was irradiated for 30 minutes to induce crosslinking of corneal collagens. It was made to be bonded. Similarly, the intraocular pressure was measured after bonding through a laser through a tonometer.
  • the intraocular pressure before and after bonding was compared to confirm whether or not the bonding was formed.
  • Hyaluronic acid and hyaluronic acid-rosebangal conjugates were dropped on the cornea of the bovine eye at 5 minute intervals for 30 minutes, and then a 532 nm laser was applied for 30 minutes to induce crosslinking of corneal collagens. Then, the corneal tissue was fixed with formalin, and the corneal tissue was stained through H&E staining, and then confirmed through a microscope.
  • the Young's modulus of the cornea was measured using an Instron device to analyze the strength of the cornea.
  • FIG. 4 shows an image of corneal tissue stained through H&E. Then, the thickness of the cornea was analyzed using the image of FIG. 4.
  • the thickness of the cornea decreased from 1000 ⁇ m to 750 ⁇ m when treated with rose bangal, and the thickness of the cornea decreased from 1000 ⁇ m to 680 ⁇ m when treated with the hyaluronic acid-rose bengal conjugate.
  • I can confirm. Through this, it can be confirmed that when the hyaluronic acid-rose bangal conjugate is used, the collagen layers of the cornea undergo more cross-linking and are more rigidly cross-linked.
  • FIG. 5 is a graph showing the length of the cornea that is stretched when the cornea is pulled at a certain intensity using the Instron device.
  • a smart contact lens equipped with an LED was manufactured as follows.
  • LED light sources For wireless control and power transmission of LED light sources, 1. Digital control, 2. Relaxation oscillator, 3. Carrier frequency generator, 4. Bandgap reference generator ), 5. A customized semiconductor device including a circuit composed of a Vdd generator is required. Using this custom-made semiconductor device, it is possible to wirelessly transmit and drive contact lenses, and control current and light irradiation timing.
  • the light source UV, blue, green, red, and infrared light emitting LEDs can be applied.
  • the ASIC device includes steps of computer simulation (the upper graph of FIG. 6A), layout generation (the diagram below FIG. 6A), and TCAD simulation (final inspection) (FIG. 6B). After that, it can be manufactured, and it was manufactured in a CMOS process of 0.18 ⁇ m or less in consideration of power consumption. In addition, the fabricated ASIC chip was mounted on a printed circuit board (PCB) board to perform final inspection.
  • PCB printed circuit board
  • a contact lens was manufactured using the custom-made semiconductor device and LED light source manufactured in (1).
  • the contact lens of the present invention was manufactured through metal deposition, photolithography, flip-chip bonding, LED bonding, and contact lens manufacturing.
  • a pad was formed using a wet/dry etching method using a photolithography process. Thereafter, using a flip-chip bonding process, the custom semiconductor device was bonded on the flexible transparent substrate by ultrasonic and thermal compression processes using a non-conductive adhesive.
  • LED light sources, batteries, capacitors for voltage and current control, and resistors were bonded using a human body compatible epoxy (Ag epoxy) in consideration of the heat resistance of the flexible plastic substrate.
  • the transparent substrate to which each element was bonded was cut only on the element part with a laser cutter, etc., and then a lens was fabricated with a human body-compatible silicon elastomer or the like.
  • the contact lens was driven through a driving board having an antenna and an RF transmission processing function.
  • FIG. 7 shows a custom semiconductor and electronic device configured on a plastic substrate.
  • FIG. 7 shows a design drawing (left view) and a photo (right photo) after flip-chip bonding on a flexible transparent substrate and Ag epoxy bonding of an LED light source.
  • a result of flip-chip bonding of the custom semiconductor device patterned-bonded on the transparent substrate can be confirmed.
  • electronic devices such as LED light sources, capacitors, batteries, and resistors using Ag epoxy, the operation status was confirmed.
  • FIG. 8 shows a manufactured smart photonic lens and a driving example.
  • the hyaluronic acid-rose bengal conjugate After applying the hyaluronic acid-rose bengal conjugate to rabbit eyes, it can be confirmed that it can be applied to damaged cornea bonding, conical cornea treatment, or vision correction by wearing a smart contact lens equipped with an LED. In addition, through thermal imaging camera analysis, it was confirmed that there was no problem in safety as the temperature change in the eyeball was less than 1°C even when the LED was driven.
  • the system according to the present invention can be used to treat damaged cornea junctions, conical corneas, cornea injuries, and the like, and can be used for a wide range of vision correction.

Abstract

The present invention relates to a system for corneal cross-linking of injured corneas, treating keratoconus, or correcting vision, the system comprising: a hyaluronic acid-dye conjugate; and a contact lens including an LED light source. In the present invention, a dye is activated by receiving light irradiated from the LED light source of the contact lens so as to generate radicals, thereby generating a covalent bond between amino acid radicals of corneal collagen, and strengthening a collagen layer. In the present invention, the hyaluronic acid-dye conjugate, in which hyaluronic acid is bound to the dye, is used to improve penetration of the dye in the cornea, and the contact lens is used together with the hyaluronic acid-dye conjugate to further improve the penetration of the dye. In addition, the structure of the lens which presses the center of the cornea deforms the shape of the cornea, thereby having a vision correction effect.

Description

LED 콘택트렌즈 및 안구용 염료를 이용한 각막 접합 및 시력교정 시스템Corneal bonding and vision correction system using LED contact lenses and eye dyes
본 발명은 LED 콘택트 렌즈 및 안구용 염료를 이용한 각막 접합 및 시력교정 시스템에 관한 것이다.The present invention relates to a corneal bonding and vision correction system using an LED contact lens and an eye dye.
원추각막은 각막의 두께가 얇아지면서 돌출되어 생기는 안질환으로 시력에 큰 영향을 미친다. 그 원인으로서 유전적 요인과 과도한 눈비빔, 자외선 노출 등이 있으며, 대비감 감소, 시력 저하, 부정 난시, 눈부심, 왜곡 등의 증상이 발생한다. 이를 치료하는 방법으로는 교정용 안경, 교정용 콘택트렌즈 착용과 같은 기구를 사용하는 방법과 각막 이식, 각막 내 링 삽입술 등과 같은 수술이 있다.Conical cornea is an eye disease caused by protruding as the thickness of the cornea becomes thin and has a great effect on vision. The causes include genetic factors, excessive irritation and exposure to ultraviolet rays, and symptoms such as decreased contrast, decreased vision, negative astigmatism, glare, and distortion. Methods of treating this include methods of using instruments such as wearing orthodontic glasses and corrective contact lenses, and surgery such as corneal transplantation and intracorneal ring insertion.
특히, 초기에는 교정용 안경 착용을 통하여 어느 정도 교정이 가능하나, 이미 일정 기간 진행 후에는 안경으로 교정이 불가능하고 원추각막 치료를 위한 하드렌즈를 착용해야한다(특허문헌 1). 상기 하드렌즈는 중앙부분이 평평하게 제작되며, 렌즈를 착용하였을 때, 착용자의 각막부분이 일시적으로 변형되어 시력을 교정할 수 있다. 특히, 근시 및 부정난시에 대한 시력교정이 가능하다. 그러나, 탈착 시 일시적으로 교정 효과가 유지되므로 영구적이지 않은 단점이 있다. 외과적 수술방법으로는 각막실질 내에 반원 형태의 고리를 삽입하여 부정난시를 줄이는 방법이나, 각막 표면을 드러내어 시술을 하는 방법이 있다. 그러나, 상기 외과적 수술방법은 환자로 하여금 이물감을 느끼게 하거나 각막을 드러내는 수술에 대한 거부감을 줄 수 있다. In particular, it is possible to correct to some extent through wearing corrective glasses at the beginning, but after a certain period of time, it is impossible to correct with glasses and a hard lens for conical cornea treatment must be worn (Patent Document 1). The hard lens has a flat central portion, and when the lens is worn, the wearer's corneal portion is temporarily deformed, so that vision can be corrected. In particular, vision correction for myopia and irregular astigmatism is possible. However, there is a disadvantage that is not permanent since the correction effect is temporarily maintained during detachment. As a surgical method, there is a method of reducing irregular astigmatism by inserting a semicircular ring in the corneal parenchyma, or a method of exposing the corneal surface to perform a procedure. However, the surgical method may make the patient feel a foreign body or give a feeling of rejection to surgery to expose the cornea.
따라서 원추각막을 효과적이고 안전하게 치료할 수 있으며, 환자에게 상시 착용 혹은 수술에 대한 부담 없는 새로운 치료, 시술 방법이 요구된다.Therefore, the conical cornea can be effectively and safely treated, and new treatments and procedures are required without the burden of regular wear or surgery to the patient.
[선행기술문헌][Prior technical literature]
[특허문헌][Patent Literature]
1. 대한민국 등록특허공보 제10-1199425호1. Korean Patent Publication No. 10-1199425
본 발명은 LED 콘택트 렌즈 및 안구용 염료를 이용한 각막 접합 및 시력교정 시스템을 제공하는 것을 목적으로 한다.An object of the present invention is to provide a corneal bonding and vision correction system using an LED contact lens and an eye dye.
본 발명은 히알루론산-염료 접합체; 및 The present invention hyaluronic acid-dye conjugate; And
LED 광원을 포함하는 콘택트렌즈를 포함하는 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템을 제공한다.It provides a system for bonding damaged cornea, conical cornea treatment, or vision correction including a contact lens including an LED light source.
본 발명은 또한, 대상의 각막에 히알루론산-염료 접합체를 적용하는 단계;The present invention also includes the steps of applying a hyaluronic acid-dye conjugate to the cornea of a subject;
LED 광원을 포함하는 콘택트렌즈를 착용하는 단계; 및 Wearing a contact lens including an LED light source; And
콘택트렌즈 내의 LED 광원에서 대상의 각막으로 빛을 조사하는 단계를 포함하는 전술한 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템을 사용한 손상된 각막 접합, 원추각막 치료 또는 시력교정 방법을 제공한다. It provides a method for bonding damaged cornea, conical cornea treatment, or vision correction using the above-described damaged cornea bonding, conical cornea treatment, or vision correction system, including the step of irradiating light from an LED light source in a contact lens to the cornea of a target.
본 발명은 히알루론산-염료 접합체; 및 LED 광원을 포함하는 콘택트렌즈를 포함하는 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템을 제공한다. The present invention hyaluronic acid-dye conjugate; And it provides a system for bonding damaged cornea, conical cornea treatment or vision correction comprising a contact lens including an LED light source.
본 발명에서 염료는 콘택트렌즈의 LED 광원에서 조사되는 빛을 받아 활성화되어 라디칼을 생성하고, 이로 인해 각막 콜라겐 사이의 아미노산 라디칼 간 공유결합을 생성하며, 콜라겐 층을 강화할 수 있다. 본 발명에서는 상기 염료에 히알루론산이 결합된 히알루론산-염료 접합체를 사용하여 염료의 각막에 대한 투과성을 향상시킬 수 있으며, 또한, 콘택트렌즈를 함께 사용하여 염료의 투과성을 보다 향상시킬 수 있다. 더욱이, 상기 콘택트렌즈는 각막의 중심을 눌러주는 구조이므로, 각막의 형태를 변형시킴으로써 시력교정 효과를 가질 수 있다.In the present invention, the dye is activated by receiving light irradiated from the LED light source of the contact lens to generate radicals, thereby generating covalent bonds between amino acid radicals between corneal collagen, and strengthening the collagen layer. In the present invention, the hyaluronic acid-dye conjugate in which hyaluronic acid is bonded to the dye may be used to improve the permeability of the dye to the cornea, and the permeability of the dye may be further improved by using a contact lens together. Moreover, since the contact lens has a structure that presses the center of the cornea, it can have a vision correction effect by changing the shape of the cornea.
본 발명에 따른 시스템은 손상된 각막 접합, 원추각막, 각막의 손상 등의 치료에 이용될 수 있으며, 크게는 전 범위적인 시력교정에도 사용될 수 있다.The system according to the present invention can be used to treat damaged cornea junctions, conical corneas, cornea injuries, and the like, and can be used for a wide range of vision correction.
도 1은 실시예에서 합성된 히알루론산-로즈뱅갈 접합체의 흡광도 분석 및 FT-IR 분석 결과를 나타낸다. 1 shows the absorbance analysis and FT-IR analysis results of the hyaluronic acid-rose bangal conjugate synthesized in Example.
도 2는 히알루론산-로즈뱅갈 접합체 및 로즈뱅갈의 각막 투과 정도를 분석한 투포톤 이미지 및 그래프를 나타낸다. 2 shows a two-photon image and graph analyzing the degree of corneal permeation of hyaluronic acid-rose bangal conjugate and rose bangal.
도 3은 로즈뱅갈과 히알루론산-로즈뱅갈 접합체를 사용하여 치료를 진행한 소 안구의 안압 변화율 및 대조군 대비 최대 안압 증가 비율을 나타낸다. 3 shows the rate of change in intraocular pressure in bovine eyes treated with rose bangal and hyaluronic acid-rose bangal conjugate and the rate of increase in maximum intraocular pressure compared to the control group.
도 4는 H&E를 통해 각막이 염색된 이미지를 통해 각막의 두께를 분석한 결과를 나타낸다. 4 shows the results of analyzing the thickness of the cornea through an image in which the cornea is stained through H&E.
도 5는 인스트론 장비를 사용하여 측정한 각막의 인장 및 가해진 세기를 나타낸다. 5 shows the tensile and applied strength of the cornea measured using the Instron instrument.
도 6a 및 b는 ASIC 소자의 제작을 나타낸 것으로, 컴퓨터 시뮬레이션, Layout, 최종검사결과를 나타낸다. 6a and b show the fabrication of an ASIC device, and show computer simulation, layout, and final inspection results.
도 7은 플라스틱 기판에 구성한 주문형 반도체 및 전자소자의 일례를 나타낸다. 7 shows an example of a custom semiconductor and electronic device configured on a plastic substrate.
도 8은 제작된 콘택트렌즈 및 구동예를 나타낸다. 8 shows a manufactured contact lens and a driving example.
본 발명은 히알루론산-염료 접합체; 및 The present invention hyaluronic acid-dye conjugate; And
LED 광원을 포함하는 콘택트렌즈를 포함하는 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템에 관한 것이다. It relates to a system for bonding damaged cornea, conical cornea treatment or vision correction, including a contact lens including an LED light source.
이하, 본 발명의 손상된 각막 접합, 원추각막 치료 또는 시력교정 시스템을 보다 상세하게 설명한다.Hereinafter, the damaged cornea junction, conical cornea treatment or vision correction system of the present invention will be described in more detail.
본 발명에서 콜라겐 결합술(각막콜라겐 교차결합술, 각막콜라겐 결합술 또는 Corneal Collagen Cross-linking라 할 수 있다.)은 약해진 각막을 강화시켜 더 이상 안구가 앞으로 밀리지 않도록 고안된 치료 방법이다. 각막은 콜라겐으로 구성된다. 콜라겐 구조물들은 따로 분리되는 것이 아닌 겹겹히 서로 맞물려 있는 구조를 가지는데, 그 구조물들의 결합력이 견고하지 못하면 각막이 원래의 모양을 유지하지 못하고 변형되게 된다. 원추각막은 이러한 결합력이 정상보다 떨어진 상태를 가진다. 따라서, 콜라겐의 결합력을 증대시켜 원추각막을 치료할 수 있다. In the present invention, collagen conjugation (can be referred to as corneal collagen cross-linking, corneal collagen cross-linking, or Corneal Collagen Cross-linking) is a treatment method designed so that the eyeball is no longer pushed forward by strengthening the weakened cornea. The cornea is made up of collagen. Collagen structures have a structure that is not separated but interlocked with each other. If the bonding strength of the structures is not strong, the cornea cannot maintain its original shape and is deformed. The conical cornea has a state in which this bonding force is less than normal. Therefore, it is possible to treat the conical cornea by increasing the binding power of collagen.
그리고, 콜라겐 결합술은 콜라겐의 결합력을 증대시키기 위해 염료를 각막내로 스며들게 한 후, 그 위에 자외선을 쬐어 주는 방법으로 진행된다. 즉, 콜라겐 결합술에서는 각막 콜라겐의 가교결합에 의해 각막 접합이 이루어질 수 있다. 이때, "가교결합"은 콜라겐 섬유 내의 분자 쇄들 간의 화학적 연결의 형성을 지칭한다. 또한, “각막 접합”은 각막 콜라겐이 가교결합을 형성하는 것을 의미한다. 상기 각막 콜라겐의 가교 결합은 약화된 각막의 기계적 특성을 증가시킬 수 있으며, 각막이 얇아지는 원추각막을 치료할 수 있다. 또한, 상기 콜라겐 결합술을 통해 시력교정 효과를 가질 수 있다. In addition, in order to increase the binding power of collagen, the collagen conjugation procedure is performed by infiltrating a dye into the cornea and then applying ultraviolet rays thereon. That is, in collagen bonding, corneal bonding may be achieved by crosslinking of corneal collagen. Here, "crosslinking" refers to the formation of chemical links between molecular chains in collagen fibers. Also, "corneal junction" means that corneal collagen forms crosslinks. The cross-linking of the corneal collagen can increase the mechanical properties of the weakened cornea, and can treat the conical cornea in which the cornea becomes thinner. In addition, it is possible to have a vision correction effect through the collagen conjugation.
본 발명에 따른 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템은 히알루론산-염료 접합체; 및 LED 광원을 포함하는 콘택트렌즈를 포함한다.Damaged cornea conjugation, conical cornea treatment or vision correction system according to the present invention is hyaluronic acid-dye conjugate; And a contact lens including an LED light source.
본 발명에서 히알루론산-염료 접합체는 히알루론산과 염료가 화학적으로 결합된 화합물이다. In the present invention, the hyaluronic acid-dye conjugate is a compound in which hyaluronic acid and a dye are chemically combined.
본 발명에서 히알루론산은 생체 적합성 및 생분해성 특성을 가질 뿐만 아니라 경피 전달 특성을 가지고 있어, 인체에 안전하게 적용할 수 있으며, 항원 단백질을 비롯한 다양한 단백질 의약품 및 화학 의약품의 경피 약물 전달 시스템에 적용 가능하다는 장점을 가진다. In the present invention, hyaluronic acid not only has biocompatibility and biodegradability, but also has transdermal delivery properties, so it can be safely applied to the human body, and can be applied to a transdermal drug delivery system of various protein drugs and chemical drugs including antigenic proteins. It has an advantage.
본 발명에서 명시적인 기재가 없는 한, '히알루론산(Hyaluronic acid, HA)'은 하기 일반식 1로 표현되는 반복단위를 갖는 고분자를 지칭하며, 히알루론산의 염 또는 유도체 형태를 모두 포함하는 의미로 사용된다.Unless explicitly stated in the present invention,'Hyaluronic acid (HA)' refers to a polymer having a repeating unit represented by the following general formula 1, and includes all salts or derivatives of hyaluronic acid. Is used.
[일반식 1][General Formula 1]
Figure PCTKR2020012280-appb-img-000001
Figure PCTKR2020012280-appb-img-000001
상기 일반식 1에서, n은 25 내지 10,000 의 정수일 수 있다.In the general formula 1, n may be an integer of 25 to 10,000.
본 발명에서 ‘히알루론산 유도체’는 상기 일반식 1의 히알루론산 기본 구조를 기반으로 하여 아민 그룹, 알데하이드 그룹, 바이닐 그룹, 치올 그룹, 알릴옥시그룹, N-숙신이미딜-3-(2-피리딜디치오)프로피오네이트(N-Succinimidyl-3-(2-pyridyldithio)propionate, SPDP), N-하이드록시숙신이미드(N-hydroxysuccinimide, NHS) 등의 작용기가 도입되어있는 히알루론산의 모든 변형체를 지칭한다. 예를 들어, 상기 히알루론산 유도체로 HA-디아미노부탄(HA-diaminobutane), HA-헥사메틸렌디아민(HA-hexamethylenediamine), HA-알데하이드(HA-aldehyde), HA-아디픽산 디하이드라지드(HA-Adipic Acid Dihydrazide, HA-ADH), HA-2-아미노에틸 메타크릴레이트 하이드로클로라이드(HA-2-Aminoethyl methacrylate hydrochloride), HA-스페르민(HA-Spermine), HA-스페르미딘(HA-spermidine), HA-SPDP 또는 HA-NHS 등을 사용할 수 있다.In the present invention, the'hyaluronic acid derivative' is an amine group, an aldehyde group, a vinyl group, a thiol group, an allyloxy group, N-succinimidyl-3-(2-pyridyl) based on the basic structure of hyaluronic acid in the general formula 1 above. All variants of hyaluronic acid in which functional groups such as dildithio) propionate (N-Succinimidyl-3-(2-pyridyldithio)propionate, SPDP) and N-hydroxysuccinimide (NHS) are introduced Refers to. For example, as the hyaluronic acid derivative, HA-diaminobutane, HA-hexamethylenediamine, HA-aldehyde, HA-adipic acid dihydrazide (HA -Adipic Acid Dihydrazide, HA-ADH), HA-2-Aminoethyl methacrylate hydrochloride, HA-Spermine, HA-spermidine (HA- spermidine), HA-SPDP, or HA-NHS.
상기 히알루론산은 대부분의 동물에 존재하며 생분해성, 생적합성, 면역반응이 없는 선형적인 다당류의 고분자로서 인체에 안전하게 적용할 수 있다. 히알루론산은 체내에서 분자량에 따라 여러 가지 다른 역할을 수행하기 때문에 여러 가지 용도로 사용될 수 있다.The hyaluronic acid is present in most animals and can be safely applied to the human body as a linear polysaccharide polymer without biodegradability, biocompatibility, or immune response. Hyaluronic acid can be used for various purposes because it plays a number of different roles depending on the molecular weight in the body.
본 발명에서 사용되는 히알루론산, 히알루론산의 염, 또는 히알루론산의 유도체는 그 구성의 한정은 없으나, 바람직하게는 분자량이 10,000 내지 3,000,000 달톤(Da)일 수 있다. 상기 범위의 분자량을 갖는 히알루론산, 또는 히알루론산의 염, 또는 히알루론산의 유도체는 약물 전달을 위한 접합체에 사용되기에 적합하다.Hyaluronic acid, a salt of hyaluronic acid, or a derivative of hyaluronic acid used in the present invention is not limited in its composition, but may preferably have a molecular weight of 10,000 to 3,000,000 Daltons (Da). Hyaluronic acid, or a salt of hyaluronic acid, or a derivative of hyaluronic acid having a molecular weight in the above range is suitable for use in conjugates for drug delivery.
본 발명에서 염료는 후술할 콘택트렌즈의 LED 광원에서 조사된 빛에 의해 라디칼을 발생시키며, 이를 통해 각막 접합이 이루어질 수 있다. In the present invention, the dye generates a radical by the light irradiated from the LED light source of the contact lens to be described later, through which corneal bonding can be achieved.
상기 염료의 종류는 특별히 제한되지 않으며, 안구용 염료를 사용할 수 있다. 상기 안구용 염료로 로즈뱅갈, 리보플라빈, 에틸 에오신, 에오신 Y, 플루오레세인, 2,2-다이메톡시, 2-페닐아세토페논, 2-메톡시, 2-페닐아세토페노노, 캄포르퀴논, 메틸렌 블루, 에리트로신, 플록심, 티오닌 및 메틸렌 그린으로 이루어진 그룹으로부터 선택된 하나 이상을 사용할 수 있다. The type of the dye is not particularly limited, and an eye dye may be used. As the eye dyes, rosebangal, riboflavin, ethyl eosin, eosin Y, fluorescein, 2,2-dimethoxy, 2-phenylacetophenone, 2-methoxy, 2-phenylacetophenono, camphorquinone, One or more selected from the group consisting of methylene blue, erythrosine, phloxime, thionine and methylene green may be used.
본 발명에서는 염료로 로즈뱅갈 또는 리보플라빈을 사용할 수 있다. 상기 리보플라빈은 354 nm의 파장의 빛을, 로즈뱅갈은 532 nm 파장의 빛을 받았을 때 활성화되어 라디칼(radical)을 형성하고, 이로 인해, 각막 콜라겐 사이의 아미노산 라디칼 간 공유결합을 생성하여 콜라겐 층을 강화할 수 있다.In the present invention, rose bangal or riboflavin may be used as a dye. The riboflavin is activated when receiving light with a wavelength of 354 nm and rose bangal with a wavelength of 532 nm, thereby forming a radical, thereby creating a covalent bond between amino acid radicals between the corneal collagen to form a collagen layer. Can be strengthened.
일 구체예에서, 히알루론산-염료 접합체는 히알루론산의 카르복실기와 염료의 카르복실기가 링커를 통해 결합된 접합체이다. In one embodiment, the hyaluronic acid-dye conjugate is a conjugate in which a carboxyl group of hyaluronic acid and a carboxyl group of a dye are bonded through a linker.
상기 링커로 디아민 화합물을 사용할 수 있으며, 상기 디아민 화합물은 디아미노헥세인(헥사메틸렌디아민), 에틸렌디아민, 부틸렌디아민, 펜타에틸렌헥사아민 및 1,5-디아미노-2-메틸펜탄로 이루어진 그룹으로부터 선택된 하나 이상일 수 있다. A diamine compound may be used as the linker, and the diamine compound is a group consisting of diaminohexane (hexamethylenediamine), ethylenediamine, butylenediamine, pentaethylenehexaamine, and 1,5-diamino-2-methylpentane It may be one or more selected from.
본 발명에서는 염료와 히알루론산을 결합시킨 히알루론산-염료 접합체를 사용하여 염료의 각막으로의 투과성을 향상시킬 수 있다. In the present invention, a hyaluronic acid-dye conjugate in which a dye and hyaluronic acid are bound may be used to improve the permeability of the dye to the cornea.
본 발명에서 콘택트렌즈는 실리콘 엘라스토머(Silicone elastomer)의 탄성중합체; 실리콘 하이드로젤(Silicone hydrogel); 폴리디메틸록산(PDMS); 폴리(2-하이드록시에틸메타크릴레이트)(PHEMA); 및 폴리에틸렌 글라이콜메타아크릴레이트(poly(ethylene glycol) methacrylate, PEGMA);로 이루어진 그룹으로부터 선택된 하나 이상의 고분자를 기반으로 할 수 있다.In the present invention, the contact lens is an elastomer of a silicone elastomer; Silicone hydrogel; Polydimethyloxane (PDMS); Poly(2-hydroxyethylmethacrylate) (PHEMA); And polyethylene glycol methacrylate (poly(ethylene glycol) methacrylate, PEGMA); It may be based on one or more polymers selected from the group consisting of.
일 구체예에서, 콘택트렌즈는 종래 시력교정용으로 사용되는 콘택트렌즈에 LED 광원을 도입한 것을 사용할 수 있으며, 또는 실험실 등에서 제조하여 사용할 있다. In one embodiment, the contact lens may be a contact lens that is conventionally used for vision correction, which incorporates an LED light source, or may be manufactured and used in a laboratory or the like.
일 구체예에서, 콘택트렌즈는 표면, 구체적으로 중앙부분이 평평한 구조를 가지며, 이에 따라 렌즈를 착용하였을 때 착용자(대상)의 각막부분이 일시적으로 변형되어 시력을 교정할 수 있다.In one embodiment, the contact lens has a structure having a flat surface, specifically, a central portion, and accordingly, when the lens is worn, the corneal portion of the wearer (target) is temporarily deformed to correct visual acuity.
본 발명에서 콘택트렌즈는 LED 광원(LED light source)을 포함한다. 본 발명에서는 이러한 광원을 콘택트렌즈에 적용시켜, 대상의 각막으로 빛을 안정적으로 조사할 수 있다. In the present invention, the contact lens includes an LED light source. In the present invention, by applying such a light source to a contact lens, it is possible to stably irradiate light to the cornea of a target.
일 구체예에서, LED 광원은 마이크로 LED(MicroLED, mLED, μLED) 일 수 있다. In one embodiment, the LED light source may be a micro LED (MicroLED, mLED, μLED).
상기 LED 광원, 즉, 마이크로 LED는 당업계에서 일반적으로 사용되는 제품을 사용할 수 있으며, 또는 직접 제작하여 사용할 수 있다. The LED light source, that is, the micro LED, may be a product generally used in the art, or may be directly manufactured and used.
일 구체예에서, LED 광원은 각막 상으로 빛을 조사할 수 있다. 상기 콘택트렌즈의 착용전 대상에 적용된 히알루론산-염료 접합체에서 염료는 상기 빛을 받아 라디칼을 생성할 수 있으며, 이를 통해 각막 콜라겐 접합을 수행할 수 있다. In one embodiment, the LED light source may irradiate light onto the cornea. In the hyaluronic acid-dye conjugate applied to the object before wearing the contact lens, the dye may receive the light to generate radicals, thereby performing corneal collagen conjugation.
일 구체예에서, LED 광원은 사용 목적에 따라 특정한 파장의 빛을 방출하는 LED 들을 선택하여 구성할 수 있다. 예를 들어, 상기 LED 광원은 350 내지 550 nm, 350 내지 380 nm 또는 520 내지 550 nm 파장의 빛을 조사할 수 있다. In one embodiment, the LED light source may be configured by selecting LEDs emitting light of a specific wavelength according to the purpose of use. For example, the LED light source may irradiate light having a wavelength of 350 to 550 nm, 350 to 380 nm, or 520 to 550 nm.
또한, 일 구체예에서, 콘택트렌즈 내의 LED 광원의 위치는 특별히 제한되지 않으며, 그 위치를 적절히 조절할 수 있다. In addition, in one embodiment, the position of the LED light source in the contact lens is not particularly limited, and the position can be appropriately adjusted.
일 구체예에서, 콘택트렌즈의 내부에는 투명기판이 형성될 수 있으며, 상기 LED 광원은 투명기판 상에 형성될 수 있다. In one embodiment, a transparent substrate may be formed inside the contact lens, and the LED light source may be formed on the transparent substrate.
상기 투명기판은 광투과성이 뛰어나고, 유연하며 신축성을 가질 수 있다. 또한, 투명기판은 생체적합성이 뛰어난 특성을 가진다. 이러한 투명기판은 파릴린 C(Parylene C), PDMS, 실리콘 엘라스토머(Silicone elastomer), 폴리에틸렌테레프탈레이트(PET) 및 폴리이미드(PI)로 이루어진 그룹으로부터 선택된 하나 이상을 포함할 수 있다. The transparent substrate may have excellent light transmittance, flexibility, and elasticity. In addition, the transparent substrate has excellent biocompatibility characteristics. The transparent substrate may include at least one selected from the group consisting of Parylene C, PDMS, silicone elastomer, polyethylene terephthalate (PET), and polyimide (PI).
일 구체예에서, LED 광원은 상기 투명기판 상에서 안구쪽 방향의 면에 형성될 수 있다. In one embodiment, the LED light source may be formed on the surface in the direction of the eyeball on the transparent substrate.
본 발명의 콘택트렌즈는 전술한 LED 광원 외에 주문형 반도체 소자(ASIC, Application Specific Integrated Circuit), 배터리 및 안테나로 이루어진 그룹으로부터 선택된 하나 이상을 추가로 포함할 수 있다. In addition to the above-described LED light source, the contact lens of the present invention may further include at least one selected from the group consisting of an application specific integrated circuit (ASIC), a battery, and an antenna.
일 구체예에서, 주문형 반도체 소자(ASIC)는 LED 광원의 무선 제어 및 전력 전송 등을 위해 사용할 수 있다. 이러한 주문형 반도체는 1. 디지털 제어(Digital control), 2. 완화 발진기(Relaxation oscillator), 3. 캐리어 주파수 발생기(Carrier frequency generator), 4. 밴드갭 기준 발생기(Bandgap reference generator), 5. Vdd 발생기(Vdd generator) 등으로 구성될 수 있다. 상기 주문형 반도체는 목적하는 용도에 맞게 제작하여 사용할 수 있다. In one embodiment, the application specific semiconductor device (ASIC) may be used for wireless control and power transmission of an LED light source. These customized semiconductors include 1. Digital control, 2. Relaxation oscillator, 3. Carrier frequency generator, 4. Bandgap reference generator, 5. Vdd generator ( Vdd generator). The custom semiconductor can be manufactured and used according to the intended use.
일 구체예에서, 배터리는 충전이 가능하고, 유연성을 가지는 박막형 배터리일 수 있다. 상기 박막형 배터리를 사용하여 콘택트렌즈의 무선 구동을 가능하게 할 수 있으며, 외부에서 파워를 공급하지 않고 동작 가능한 시스템을 구현할 수도 있다. In one embodiment, the battery may be a rechargeable, flexible thin-film battery. Using the thin-film battery, it is possible to wirelessly drive a contact lens, and a system capable of operating without supplying power from the outside may be implemented.
상기 배터리는 콘택트렌즈를 구성하고 있는 소자들에 전력을 공급할 수 있다. 또한, 반복적인 구부림 또는 변형에도 배터리의 파손이 없고, 렌즈에 적용하였을 시에 밀봉이 되며 안구 내 안정성을 확보할 수 있다. 상기 박막형 배터리는 당업계에서 사용되는 제품을 사용할 수 있으며, 직접 제작하여 사용할 수 있다. The battery may supply power to elements constituting the contact lens. In addition, there is no damage to the battery even when repeatedly bent or deformed, and when applied to a lens, it is sealed, and intraocular stability can be secured. The thin-film battery may be a product used in the art, and may be directly manufactured and used.
일 구체예에서, 안테나는 유도전류 및 전자기 공명을 통하여 전력 및 신호를 외부로 송신 및 수신할 수 있다. 상기 안테나는 원형의 구조를 가지는 원형 안테나일 수 있다. In one embodiment, the antenna may transmit and receive power and signals to the outside through induced current and electromagnetic resonance. The antenna may be a circular antenna having a circular structure.
상기 안테나는 나노물질로 구성될 수 있으며, 상기 나노물질은 금속 박막물질; 나노입자인 0차원 물질; 나노와이어, 나노 파이버 또는 나노튜브인 1차원 나노물질; 및 그래핀, MoS 2 또는 나노 플레이크인 2차원 나노물질로 이루어진 그룹으로부터 선택된 하나 이상을 포함할 수 있다. 구체적으로, 안테나는 은 나노와이어 또는 은-금 코어쉘 나노와이어(Ag@Au core-shell NW)를 포함할 수 있다. The antenna may be made of a nanomaterial, and the nanomaterial may include a metal thin film material; 0-dimensional material that is a nanoparticle; One-dimensional nanomaterials such as nanowires, nanofibers, or nanotubes; And graphene, MoS 2 or may include one or more selected from the group consisting of two-dimensional nanomaterials that are nanoflakes. Specifically, the antenna may include a silver nanowire or a silver-gold core-shell nanowire (Ag@Au core-shell NW).
일 구체예에서, 안테나는 외부에서 발생된 파워, 즉, 무선 전력을 수신하기 위한 무선전기 안테나 및 데이터 통신을 위한 radio frequency 안테나로 구성될 수 있다. In one embodiment, the antenna may be composed of a wireless electric antenna for receiving externally generated power, that is, wireless power, and a radio frequency antenna for data communication.
특히, 본 발명에서는 무선전기 안테나를 사용하여, 배터리의 역할을 보완할 수 있다. 상기 무선전기 안테나는 후술할 스마트 안경의 무선 전기 코일에서 발생된 파워를 수신할 수 있다. 상기 수신된 파워는 주문형 반도체 소자의 제어를 통해 LED 광원의 구동 등에 사용할 수 있다. In particular, in the present invention, the role of the battery can be supplemented by using a wireless electric antenna. The wireless electric antenna may receive power generated from a wireless electric coil of smart glasses, which will be described later. The received power can be used for driving an LED light source through control of an on-demand semiconductor device.
일 구체예에서, 전술한 주문형 반도체 소자, 배터리 및 안테나는 투명기판 상에 형성되어 제작 및 구동을 용이하게 할 수 있다. 상기 주문형 반도체 소자, 배터리 및 안테나는 투면기판 상에서 안구쪽 방향의 면, 즉, LED 광원과 동일한 면에 형성될 수 있다.In one embodiment, the above-described customized semiconductor device, battery, and antenna may be formed on a transparent substrate to facilitate manufacturing and driving. The custom semiconductor device, the battery, and the antenna may be formed on the transparent substrate in the direction of the eyeball, that is, on the same surface as the LED light source.
본 발명에서 LED 광원을 포함하는 콘택트렌즈는 (S1) 핸들링 기판 상에 물에 용해되는 희생층을 형성하는 단계;In the present invention, the contact lens including the LED light source comprises the steps of (S1) forming a sacrificial layer dissolved in water on a handling substrate;
(S2) 상기 희생층 상에 투명기판을 형성하는 단계;(S2) forming a transparent substrate on the sacrificial layer;
(S3) 상기 투명기판 상에 LED 광원을 형성하는 단계; 및 (S3) forming an LED light source on the transparent substrate; And
(S4) 상기 LED 광원이 형성된 투명기판을 콘택트렌즈 내로 전사시키는 단계를 통해 제조될 수 있다. (S4) It may be manufactured through the step of transferring the transparent substrate on which the LED light source is formed into a contact lens.
단계 (S1)은 핸들링 기판(handling substrate) 상에 희생층을 형성하는 단계이다. Step (S1) is a step of forming a sacrificial layer on a handling substrate.
상기 희생층은 핸들링 기판과 투명기판 사이의 접착층의 역할을 수행할 수 있으며, LED 광원이 형성된 투명기판의 전사(transfer)를 도울 수 있다. 이러한 희생층은 물에 용해될 수 있다면 특별히 제한되지 않으며, 폴리비닐알코올(PVA) 및 덱스트란(DEXTRAN)으로 이루어진 그룹으로부터 선택된 하나 이상을 포함할 수 있다. The sacrificial layer may serve as an adhesive layer between the handling substrate and the transparent substrate, and may help transfer the transparent substrate on which the LED light source is formed. This sacrificial layer is not particularly limited as long as it can be dissolved in water, and may include at least one selected from the group consisting of polyvinyl alcohol (PVA) and dextran (DEXTRAN).
단계 (S2)는 희생층 상에 투명기판을 형성하는 단계로서, 희생층은 접착제의 역할을 수행한다. 따라서, 상기 투명기판은 핸들링 기판과 용이하게 부착될 수 있으며, 추후 공정에서 희생층의 용해를 통해 핸들링 기판과 용이하게 박리될 수 있다. Step (S2) is a step of forming a transparent substrate on the sacrificial layer, the sacrificial layer serves as an adhesive. Accordingly, the transparent substrate can be easily attached to the handling substrate, and can be easily separated from the handling substrate through the dissolution of the sacrificial layer in a later process.
일 구체예에서 투명기판은 광투과성이 뛰어난 재료를 사용할 수 있으며, 전술한 종류를 사용할 수 있다. In one embodiment, the transparent substrate may be made of a material having excellent light transmittance, and the above-described type may be used.
단계 (S3)는 투명기판 상에 LED 광원을 형성하는 단계이다. Step (S3) is a step of forming an LED light source on a transparent substrate.
일 구체예에서, LED 광원은 인체 적합성 에폭시, 예를 들어, Ag epoxy 등을 사용하여 투명기판에 접합시킬 수 있다. In one embodiment, the LED light source may be bonded to the transparent substrate using a human body compatible epoxy, for example, Ag epoxy.
또한, 단계 (S4)는 LED 광원이 형성된 투명기판을 콘택트렌즈 내로 전사시키는 단계이다. In addition, step (S4) is a step of transferring the transparent substrate on which the LED light source is formed into the contact lens.
희생층 상에 제작된 LED 광원은 생체친화적인 물에서 희생층을 녹이면서 전사(fransfer)될 수 있다. The LED light source fabricated on the sacrificial layer can be transferred while melting the sacrificial layer in biocompatible water.
또한, 본 발명은 투명기판 상에 주문형 반도체 소자, 베터리 및 안테나를 형성하는 단계를 추가로 포함할 수 있다. 상기 단계는 단계 (S3)의 수행시 수행될 수 있다.In addition, the present invention may further include forming an on-demand semiconductor device, a battery, and an antenna on a transparent substrate. This step may be performed when performing step (S3).
일 구체예에서, 주문형 반도체 소자는 투명기판에 금 혹은 알루미늄 등의 금속을 증착한 후, 포토리소그래피 공정을 이용한 식각 방법을 통해 금속 패드를 형성하는 단계; 및 In one embodiment, the on-demand semiconductor device includes depositing a metal such as gold or aluminum on a transparent substrate, and then forming a metal pad through an etching method using a photolithography process; And
상기 금속 패드에 플립-칩 본딩 공정을 통해 소자를 접합하는 단계를 통해 제조될 수 있다. It may be manufactured by bonding the device to the metal pad through a flip-chip bonding process.
상기 플립-칩 본딩 공정에서는 비전도성 접착제를 이용하여 초음파 및 열 압착 공정을 통해 소자를 본딩할 수 있다. In the flip-chip bonding process, the device may be bonded through an ultrasonic and thermal compression process using a non-conductive adhesive.
일 구체예에서, 배터리는 LED 광원과 같은 방법으로 투명기판에 형성될 수 있다. In one embodiment, the battery may be formed on the transparent substrate in the same manner as the LED light source.
또한, 일 구체예에서, 안테나는 (a1) 투명기판 상에 패터닝을 위한 마스크 물질을 형성하는 단계;In addition, in one embodiment, the antenna comprises the steps of: (a1) forming a mask material for patterning on a transparent substrate;
(a2) 상기 마스크 물질이 형성된 투명기판에 나노물질을 리프트-오프 공정을 통해 코팅하여 센서 및 회로를 패터닝하는 단계; 및 (a2) patterning a sensor and a circuit by coating a nanomaterial on the transparent substrate on which the mask material is formed through a lift-off process; And
(a3) 상기 패터닝된 센서 및 회로 상에 패시베이션층을 형성하는 단계를 통해 제조될 수 있다. (a3) It may be manufactured through the step of forming a passivation layer on the patterned sensor and circuit.
단계 (a1)는 투명기판 상에 패터닝을 위한 마스크 물질을 형성하는 단계이다. Step (a1) is a step of forming a mask material for patterning on a transparent substrate.
상기 마스크 물질은 쉐도우 마스크의 역할을 수행할 수 있으며, 마스크 물질의 사용을 통해 나노물질을 패터닝할 수 있다. 이러한 마스크 물질로 포토레지스트(Photoresist)로 사용할 수 있는 물질을 사용할 수 있으며, 구체적으로 LOF, AZ 시리즈 등을 사용할 수 있다.The mask material may serve as a shadow mask, and the nanomaterial may be patterned through the use of the mask material. As such a mask material, a material that can be used as a photoresist may be used, and specifically, LOF, AZ series, and the like may be used.
단계 (a2)는 마스크 물질이 형성된 투명기판에 나노물질을 리프트-오프 공정을 통해 코팅하여 센서 및 회로를 패터닝하는 단계이다. Step (a2) is a step of patterning a sensor and a circuit by coating a nanomaterial on a transparent substrate on which a mask material is formed through a lift-off process.
상기 단계를 통해 나노물질의 패턴을 형성할 수 있다. 상기 나노물질은 전술한 종류를 사용할 수 있으며, 구체적으로 은 나노와이어 또는 은-금 코어쉘 나노와이어(Ag@Au core-shell NW)를 사용할 수 있다. Through the above step, a pattern of nanomaterials may be formed. As the nanomaterials, the above-described types may be used, and specifically, silver nanowires or silver-gold core-shell nanowires (Ag@Au core-shell NW) may be used.
상기 단계에서 제조되는 나노물질은 안테나로서 작용할 수 있다. The nanomaterial prepared in the above step may function as an antenna.
또한, 상기 단계에서 제조된 회로는 LED 광원, 반도체 소자, 안테나 및 배터리를 연결하는 역할을 수행할 수 있다. In addition, the circuit manufactured in the above step may serve to connect an LED light source, a semiconductor device, an antenna, and a battery.
단계 (a3)는 상기 패터닝된 안테나 및 회로 상에 패시베이션층을 형성하는 단계이다. Step (a3) is a step of forming a passivation layer on the patterned antenna and circuit.
상기 페시베이션층을 형성하여 나노물질의 유실을 방지하고 전기적 안정성을 향상시킬 수 있다.By forming the passivation layer, loss of nanomaterials may be prevented and electrical stability may be improved.
또한, 본 발명의 시스템은 스마트 안경을 추가로 포함할 수 있다. In addition, the system of the present invention may further include smart glasses.
본 발명에서 스마트 안경은 무선으로 전기적인 신호를 송신 또는 수신하여 상기 콘택트렌즈의 LED 광원의 구동을 조절할 수 있다. 상기 스마트 안경의 구동전원은 충전이 가능한 리튬 이온배터리를 사용할 수 있으며, 스마트 안경에 있는 bluetooth 모듈을 이용하여 스마트 기기와 무선통신을 수행할 수 있다.In the present invention, the smart glasses may control driving of the LED light source of the contact lens by transmitting or receiving an electrical signal wirelessly. The driving power of the smart glasses may use a rechargeable lithium-ion battery, and wireless communication with a smart device may be performed using a bluetooth module in the smart glasses.
상기 스마트 안경은 스마트폰, 스마트 시계 또는 PC와 페어링될 수 있다. 파워는 내장된 리튬 이온전지를 사용할 수 있으며, 자가 파워링을 위해 포토셀이 삽입될 수 있다. 상기 스마트 안경의 총 무게는 20g 미만이며, Wi-Fi 802.11b/g, Bluetooth, micro USB가 가능할 수 있다.The smart glasses may be paired with a smartphone, a smart watch, or a PC. The built-in lithium ion battery can be used for power, and a photocell can be inserted for self-powering. The total weight of the smart glasses is less than 20g, and Wi-Fi 802.11b/g, Bluetooth, and micro USB may be possible.
본 발명에 따른 시스템은 손상된 각막의 접합에 사용될 수 있으며, 원추각막의 치료에 사용될 수 있다. 또한, 시력교정에 사용될 수 있다. The system according to the invention can be used for the bonding of damaged corneas and for the treatment of conical corneas. It can also be used for vision correction.
또한, 본 발명은 전술한 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템을 사용한 손상된 각막 접합, 원추각막 치료 또는 시력교정 방법에 관한 것이다. In addition, the present invention relates to a method for conical cornea bonding, conical cornea treatment, or vision correction using the above-described damaged cornea bonding, conical cornea treatment or vision correction system.
본 발명에 따른 방법은 (A) 대상의 각막에 히알루론산-염료 접합체를 적용하는 단계;The method according to the present invention comprises the steps of (A) applying a hyaluronic acid-dye conjugate to the cornea of a subject;
(B) LED 광원을 포함하는 콘택트렌즈를 착용하는 단계; 및 (B) wearing a contact lens including an LED light source; And
(C) 콘택트렌즈 내의 LED 광원에서 대상의 각막으로 빛을 조사하는 단계를 포함한다. (C) irradiating light from the LED light source in the contact lens to the cornea of the target.
단계 (A)는 대상의 각막에 히알루론산-염료 접합체를 적용하는 단계이다. 상기 히알루론산-염료 접합체는 액상의 조성물인 점안제 형태로 제조되어, 각막에 적하(로딩)시키는 방법으로 상기 각막에 적용될 수 있다. Step (A) is a step of applying a hyaluronic acid-dye conjugate to the cornea of a subject. The hyaluronic acid-dye conjugate is prepared in the form of an eye drop, which is a liquid composition, and can be applied to the cornea by dropping (loading) it onto the cornea.
기존의 안구용 염료는 각막의 표층(corneal epithelial layer)을 수술로 제거한 뒤에 각막 실질 영역에 직접적으로 투여된다. 본 발명에서는 안구용 염료에 히알루론산을 결합시켜 각막의 표층을 제거하는 수술 없이 염료를 각막에 적용시킬 수 있다. 상기 접합체는 각막의 표층을 투과하여 콜라겐이 많이 분포하고 있는 각막 실질(corneal stroma)까지 성공적으로 전달될 수 있으며, 따라서 각막에 대한 높은 투과성을 가질 수 있다. Existing eye dyes are administered directly to the corneal parenchyma after surgical removal of the corneal epithelial layer. In the present invention, the dye can be applied to the cornea without surgery to remove the surface layer of the cornea by binding hyaluronic acid to the eye dye. The conjugate penetrates the surface layer of the cornea and can be successfully delivered to the corneal stroma where a large amount of collagen is distributed, and thus, can have high permeability to the cornea.
단계 (B)는 LED 광원을 포함하는 콘택트렌즈를 착용하는 단계이다. 본 발명에 따른 LED 광원을 포함하는 콘택트렌즈는 종래의 시력교정용 렌즈와 같은 구조를 가질 수 있으며, 구체적으로 중앙부분이 평평할 수 있다. 이를 통해, 렌즈를 착용하였을 때, 각막의 중심을 눌러주는 구조가 되어 각막의 형태를 변형시켜 시력교정에 효과가 있다. 또한 히알루론산-염료 접합체를 각막 표면에 로딩하고 콘택트렌즈 착용하였을 때, 착용 압력으로 인해 히알루론산-염료가 각막 실질 영역까지 더 잘 투과되도록 할 수 있다. Step (B) is a step of wearing a contact lens including an LED light source. The contact lens including the LED light source according to the present invention may have the same structure as a conventional lens for vision correction, and specifically, a central portion may be flat. Through this, when the lens is worn, it becomes a structure that presses the center of the cornea, thereby deforming the shape of the cornea, which is effective in correcting vision. In addition, when the hyaluronic acid-dye conjugate is loaded on the corneal surface and the contact lens is worn, the hyaluronic acid-dye can be better transmitted to the corneal parenchyma due to the wearing pressure.
단계 (C)는 콘택트렌즈 내의 LED 광원에서 대상의 각막으로 빛을 조사하는 단계이다. Step (C) is a step of irradiating light from the LED light source in the contact lens to the cornea of the target.
상기 단계를 통해, 염료는 콘택트렌즈의 LED 광원에서 조사되는 빛을 받아 활성화되어 라디칼을 생성하고, 이로 인해 각막 콜라겐 사이의 아미노산 라디칼 간 공유결합을 생성하며, 콜라겐 층을 강화할 수 있다. Through the above step, the dye is activated by receiving light irradiated from the LED light source of the contact lens to generate radicals, thereby generating covalent bonds between amino acid radicals between corneal collagen, and strengthening the collagen layer.
특히, 본 발명에서는 히알루론산-염료 접합체를 사용하고, 표면이 평평한 콘택트렌즈를 사용함으로써, LED 광원을 통해 각막 쪽으로 특정 파장의 빛을 조사하여 각막 콜라겐층의 더욱 효과적인 가교를 유도할 수 있으며, 이로 인해 시력교정의 효과를 기존보다 연장시킬 수 있다.In particular, in the present invention, by using a hyaluronic acid-dye conjugate and using a contact lens having a flat surface, light of a specific wavelength can be irradiated toward the cornea through an LED light source to induce more effective crosslinking of the corneal collagen layer. Therefore, the effect of vision correction can be extended than before.
일 구체예에서, LED 광원에서 조사되는 빛의 파장은 350 내지 550 nm, 350 내지 380 nm 또는 520 내지 550 nm일 수 있다. 조사 시간은 광량에 따라 달라질 수 있으며, 예를 들어, 200 내지 800 초일 수 있다. In one embodiment, the wavelength of light irradiated from the LED light source may be 350 to 550 nm, 350 to 380 nm, or 520 to 550 nm. The irradiation time may vary depending on the amount of light, and may be, for example, 200 to 800 seconds.
일 구체예에서, 본 발명의 방법은 스마트 안경을 추가로 사용할 수 있다. 상기 스마트 안경의 무선 전기 코일에서 발생된 파워인 무선 전력은 콘택트렌즈의 무선전기 안테나에서 수신되고, 주문형 반도체 소자의 제어를 통해 수신된 파워를 LED 광원의 구동에 사용할 수 있다.In one embodiment, the method of the present invention may additionally use smart glasses. The wireless power, which is the power generated from the wireless electric coil of the smart glasses, is received from the wireless electric antenna of the contact lens, and the power received through the control of the customized semiconductor element can be used to drive the LED light source.
이하, 본 발명을 하기 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited to the following examples.
실시예. Example.
실시예 1. 히알루론산이 접합된 안구용 염료 제조Example 1. Preparation of eye dye conjugated with hyaluronic acid
히알루론산(100 kDa) 500 mg 및 디아미노헥세인 2.89 g을 pH 4.8인 소듐 아세테이트(sodium acetate) 버퍼에 넣고 EDC(1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide)를 첨가하여 5 분간 반응을 진행하였다. 500 mg of hyaluronic acid (100 kDa) and 2.89 g of diaminohexane were added to a sodium acetate buffer with a pH of 4.8, and EDC (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide) was added to react for 5 minutes. Proceeded.
그 다음, 로즈뱅갈을 디아미노헥세인의 몰농도의 2 배수로 첨가하고, EDC와 N-하이드록시숙신이미드(N-hydroxysuccinimid)를 과량 첨가하였다. 염산과 수산화나트륨으로 용액의 pH를 4.8로 유지시키면서 12 시간 동안 상온에서 반응을 진행시켰다. 증류수에 일주일간 정제시킨 뒤, 최종 용액을 3 일 동안 동결 건조시켜, 히알루론산-로즈뱅갈 접합체를 제조하였다.Then, rosebangal was added in twice the molar concentration of diaminohexane, and EDC and N-hydroxysuccinimid were added in excess. The reaction was carried out at room temperature for 12 hours while maintaining the pH of the solution at 4.8 with hydrochloric acid and sodium hydroxide. After purification in distilled water for a week, the final solution was freeze-dried for 3 days to prepare a hyaluronic acid-rose bangal conjugate.
실험예 1. 히알루론산-로즈뱅갈 접합체 제조 확인Experimental Example 1. Confirmation of preparation of hyaluronic acid-rose bangal conjugate
1) 방법1) method
실시예 1에서 합성된 히알루론산-로즈뱅갈 접합체의 확인을 위해, 제조된 접합체의 흡광도 및 FT-IR 분석을 진행하였다.To confirm the hyaluronic acid-rosebangal conjugate synthesized in Example 1, absorbance and FT-IR analysis of the prepared conjugate were performed.
2) 결과2) result
도 1은 히알루론산-로즈뱅갈 접합체의 흡광도 및 FT-IR 분석 결과를 나타낸다.1 shows the absorbance and FT-IR analysis results of the hyaluronic acid-rose bangal conjugate.
먼저, 도 1의 위의 그래프는 히알루론산-로즈뱅갈 접합체의 흡광도를 나타낸 것으로, 로즈뱅갈 자체 픽이 540 nm에서 580 nm로 치환된 것을 확인할 수 있다. 또한, 도 1의 아래 그래프는 순수 로즈뱅갈(왼쪽) 및 히알루론산-로즈뱅갈 접합체(오른쪽)의 FT-IR 분석 결과를 나타낸 것으로, 순수 로즈뱅갈에서는 관찰되지 않는 픽이 3000 nm 부근에서 관찰되는 것을 확인할 수 있다. 이를 통해, 히알루론산-로즈뱅갈 접합체가 성공적으로 합성되었음을 확인할 수 있다. First, the above graph of FIG. 1 shows the absorbance of the hyaluronic acid-rose bengal conjugate, and it can be seen that the rose bengal's own pick has been substituted from 540 nm to 580 nm. In addition, the graph below of FIG. 1 shows the results of FT-IR analysis of pure rose bangal (left) and hyaluronic acid-rose bangal conjugate (right), showing that a pick that is not observed in pure rose bangal is observed near 3000 nm. I can confirm. Through this, it can be confirmed that the hyaluronic acid-rosebangal conjugate was successfully synthesized.
실험예 2. 히알루론산-로즈뱅갈 접합체의 안구 각막 투과율 분석Experimental Example 2. Analysis of eye corneal transmittance of hyaluronic acid-rose bangal conjugate
1) 방법1) method
실시예 1에서 합성된 히알루론산-로즈뱅갈 접합체를 소 안구 각막에 30 분 동안 5 분 간격으로 떨어뜨렸다. 비교군으로 순수 로즈뱅갈 용액을 같은 방법으로 떨어뜨렸다. The hyaluronic acid-rosebangal conjugate synthesized in Example 1 was dropped on the bovine ocular cornea at 5 minute intervals for 30 minutes. As a control group, a pure rose-bangal solution was dropped in the same way.
그 후, 소 안구에서 각막을 적출하여 투포톤 이미지 분석을 수행하였다. Thereafter, the cornea was removed from the bovine eye to perform a two-photon image analysis.
2) 결과2) result
도 2는 히알루론산-로즈뱅갈 접합체(HA-RB) 및 로즈뱅갈(Rose Bengal)의 각막 투과 정도를 나타내는 사진 및 그래프이다. 2 is a photograph and graph showing the degree of corneal permeation of hyaluronic acid-rose bengal conjugate (HA-RB) and rose bengal.
상기 도 2에 나타난 바와 같이, 히알루론산-로즈뱅갈 접합체를 사용한 경우 620 μm까지 형광을 보였으며, 로즈뱅갈을 사용한 경우 400 μm까지 형광을 보이는 것을 확인할 수 있다. 이를 통해, 로즈뱅갈에 히알루론산이 접합될 경우 각막에 대한 투과율이 더욱 높아지는 것을 확인할 수 있다. As shown in FIG. 2, when the hyaluronic acid-rose bangal conjugate was used, fluorescence was exhibited up to 620 μm, and when rose bangal was used, fluorescence was displayed up to 400 μm. Through this, it can be seen that when hyaluronic acid is conjugated to rose bangal, the transmittance to the cornea is further increased.
실험예 3. 히알루론산-로즈뱅갈 접합체를 통한 각막 접합 분석Experimental Example 3. Analysis of corneal junction through hyaluronic acid-rose bangal conjugate
1) 방법1) method
소 안구 각막에 0.4 cm 가량의 상처를 유도한 뒤, 소 안구 내부의 압력을 안압계를 통해 측정하였다. 그 다음, 상처를 유도한 해당 영역에 30 분 동안 5분 간격으로 히알루론산-로즈뱅갈 접합체 용액 및 로즈뱅갈 용액을 각각 떨어뜨리고, 532 nm의 레이저를 30 분간 쪼여줌으로써 각막 콜라겐끼리의 가교를 유도하여 접합되도록 하였다. 마찬가지로 안압계를 통해 레이저를 통해 접합시킨 뒤의 안압을 측정하였다. After inducing a wound of about 0.4 cm in the bovine eye cornea, the pressure inside the bovine eye was measured through a tonometer. Then, the hyaluronic acid-rose bengal conjugate solution and the rose bengal solution were respectively dropped on the affected area in which the wound was induced, and the 532 nm laser was irradiated for 30 minutes to induce crosslinking of corneal collagens. It was made to be bonded. Similarly, the intraocular pressure was measured after bonding through a laser through a tonometer.
접합되기 전과 접합된 후의 안압을 비교하여 접합의 형성 여부를 확인하였다. The intraocular pressure before and after bonding was compared to confirm whether or not the bonding was formed.
2) 결과2) result
도 3은 히알루론산-로즈뱅갈 접합체 용액 및 로즈뱅갈 용액으로 치료를 한 소 안구에서의 안압의 변화율을 나타낸다. 3 shows the rate of change in intraocular pressure in bovine eyes treated with hyaluronic acid-rose bangal conjugate solution and rose bangal solution.
상기 도 3에 나타난 바와 같이, 로즈뱅갈을 처리하였을 때 안구 내 최대 안압은 처리하지 않았을 경우 대배 약 2 배 가량 증가하였으며, 히알루론산-로즈뱅갈 접합체를 처리하였을 때에는 약 3.5배의 상승률을 보이는 것을 확인할 수 있다. 이를 통해, 히알루론산-로즈뱅갈 접합체를 처리하였을 때 더 효율적인 각막 접합이 가능함을 확인할 수 있다. As shown in FIG. 3, when the rose bangal was treated, the maximum intraocular pressure was increased by about 2 times when not treated, and when the hyaluronic acid-rose bangal conjugate was treated, it showed an increase rate of about 3.5 times. I can. Through this, it can be confirmed that more efficient corneal conjugation is possible when the hyaluronic acid-rose bangal conjugate is treated.
실험예 4. 히알루론산-로즈뱅갈 접합체를 통한 각막 성형 및 강도 변화 분석Experimental Example 4. Analysis of corneal shaping and strength change through hyaluronic acid-rose bangal conjugate
1) 방법1) method
소 안구 각막에 히알루론산, 히알루론산-로즈뱅갈 접합체를 각각 30 분 동안 5 분 간격으로 떨어뜨린 뒤, 30 분 간 532 nm 레이저를 쬐어주어 각막 콜라겐끼리의 가교를 유도하였다. 그 뒤, 각막 조직을 포르말린으로 고정시키고 H&E 염색을 통해 각막 조직을 염색한 뒤 현미경을 통해 확인하였다. Hyaluronic acid and hyaluronic acid-rosebangal conjugates were dropped on the cornea of the bovine eye at 5 minute intervals for 30 minutes, and then a 532 nm laser was applied for 30 minutes to induce crosslinking of corneal collagens. Then, the corneal tissue was fixed with formalin, and the corneal tissue was stained through H&E staining, and then confirmed through a microscope.
또한, 콜라겐끼리의 가교가 유도된 소 안구 각막을 적출해 낸 뒤, 인스트론 장비를 이용하여 각막의 영률(Young’s modulus)을 측정하여 각막의 강도를 분석하였다.In addition, after the bovine ocular cornea in which the crosslinking between collagens was induced was excised, the Young's modulus of the cornea was measured using an Instron device to analyze the strength of the cornea.
2) 결과2) result
도 4는 H&E를 통해 염색된 각막 조직의 이미지를 나타낸다. 그리고, 상기 도 4의 이미지를 사용하여 각막의 두께를 분석하였다. 4 shows an image of corneal tissue stained through H&E. Then, the thickness of the cornea was analyzed using the image of FIG. 4.
상기 도 4에 나타난 바와 같이, 로즈뱅갈을 처리할 경우 각막의 두께가 1000 μm에서 750 μm로 감소하였으며, 히알루론산-로즈뱅갈 접합체를 처리하였을 경우 상기 각막의 두께가 1000 μm에서 680 μm로 감소한 것을 확인할 수 있다. 이를 통해, 히알루론산-로즈뱅갈 접합체를 사용할 경우 각막의 콜라겐 층끼리 더 가교가 잘 진행되어 더 단단하게 가교되는 것을 확인할 수 있다.As shown in FIG. 4, the thickness of the cornea decreased from 1000 μm to 750 μm when treated with rose bangal, and the thickness of the cornea decreased from 1000 μm to 680 μm when treated with the hyaluronic acid-rose bengal conjugate. I can confirm. Through this, it can be confirmed that when the hyaluronic acid-rose bangal conjugate is used, the collagen layers of the cornea undergo more cross-linking and are more rigidly cross-linked.
한편, 도 5는 인스트론 장비를 이용하여 각막을 일정한 세기로 당겼을 때 늘어나는 길이를 그래프를 표시한 것이다. Meanwhile, FIG. 5 is a graph showing the length of the cornea that is stretched when the cornea is pulled at a certain intensity using the Instron device.
상기 도 5에 나타난 바와 같이, 영률 분석 결과, 접합체를 처리하지 않은 비교군(Control)의 경우 1.76, 로즈뱅갈을 처리한 경우 2.75, 그리고 히알루론산-로즈뱅갈 접합체를 처리한 경우 3.1의 영률 값을 보이는 것을 확인할 수 있다. 이를 통해, 히알루론산-로즈뱅갈 접합체를 처리하였을 때 실제로 각막 콜라겐 층 간의 결합이 이루어지며 더 단단해지는 것을 확인할 수 있다.As shown in FIG. 5, as a result of the Young's modulus analysis, the Young's modulus value of 1.76 in the case of the control group not treated with the conjugate, 2.75 in the case of treatment with rose bangal, and 3.1 when the hyaluronic acid-rose bangal conjugate was treated. You can see what you see. Through this, it can be confirmed that when the hyaluronic acid-rose bangal conjugate is treated, the bonding between the corneal collagen layers is actually made, and it becomes harder.
실시예 2. 콘택트 렌즈 제조Example 2. Manufacture of contact lenses
실시예 1의 히알루론산-염료 접합체를 이용한 손상된 각막 접합, 원추각막 치료 또는 시력교정을 위한 광원으로서, LED가 장착된 스마트 콘택트렌즈를 하기와 같이 제작하였다.As a light source for bonding damaged corneas, conical cornea treatment or vision correction using the hyaluronic acid-dye conjugate of Example 1, a smart contact lens equipped with an LED was manufactured as follows.
(1) 주문형 반도체(ASIC) 설계 및 제작(1) Design and manufacture of customized semiconductor (ASIC)
LED 광원의 무선 제어 및 전력 전송을 위하여, 1. 디지털 제어(Digital control), 2. 완화 발진기(Relaxation oscillator), 3. 캐리어 주파수 발생기(Carrier frequency generator), 4. 밴드갭 기준 발생기(Bandgap reference generator), 5. Vdd 발생기(Vdd generator) 등으로 구성된 회로가 포함된 주문형 반도체 소자가 필요하다. 본 주문형 반도체 소자를 사용하여 콘택트렌즈의 무선 전력 전달 및 구동이 가능하며, 전류 및 광 조사 타이밍의 제어가 가능하다. 광원은 자외선, 청색, 녹색, 적색, 적외선 발광 LED를 적용할 수 있다. For wireless control and power transmission of LED light sources, 1. Digital control, 2. Relaxation oscillator, 3. Carrier frequency generator, 4. Bandgap reference generator ), 5. A customized semiconductor device including a circuit composed of a Vdd generator is required. Using this custom-made semiconductor device, it is possible to wirelessly transmit and drive contact lenses, and control current and light irradiation timing. As the light source, UV, blue, green, red, and infrared light emitting LEDs can be applied.
상기 주문형 반도체(ASIC) 소자는 도 6에 나타난 바와 같이, 컴퓨터 시뮬레이션(도 6a 윗 그래프), 레이아웃 생성(Layout generation)(도 6a 아래 도면) 및 TCAD 시뮬레이션(최종검사)(도 6b)의 단계를 거쳐 제작이 가능하며, 자체소비전력을 고려하여 CMOS 0.18 μm 이하의 공정으로 제작하였다. 그리고, 제작된 ASIC 칩을 PCB(printed circuit board) 보드에 실장하여 최종 검사를 진행하였다. As shown in FIG. 6, the ASIC device includes steps of computer simulation (the upper graph of FIG. 6A), layout generation (the diagram below FIG. 6A), and TCAD simulation (final inspection) (FIG. 6B). After that, it can be manufactured, and it was manufactured in a CMOS process of 0.18 μm or less in consideration of power consumption. In addition, the fabricated ASIC chip was mounted on a printed circuit board (PCB) board to perform final inspection.
(2) 콘택트 렌즈 제조(2) Contact lens manufacturing
(1)에서 제작된 주문형 반도체 소자 및 LED 광원을 사용하여 콘택트렌즈를 제조하였다. A contact lens was manufactured using the custom-made semiconductor device and LED light source manufactured in (1).
본 발명의 콘택트렌즈는 금속 증착(Metal Deposition), 포토리소그래피(Photolithography), 플립-칩 본딩(Flip Chip Bonding), LED 본딩(LED Bonding) 및 콘택트렌즈 제조(Contact Lens) 공정을 통해 제조되었다. The contact lens of the present invention was manufactured through metal deposition, photolithography, flip-chip bonding, LED bonding, and contact lens manufacturing.
구체적으로, 30 μm 이하의 유연성 투명기판에 금 혹은 알루미늄 등의 금속을 200 내지 500 nm로 증착한 후, 포토리소그래피 공정을 이용한 습/건식 식각 방법을 이용하여 패드를 형성하였다. 그 후, 플립-칩 본딩(Flip-Chip bonding) 공정을 사용하여, 상기 유연성 투명기판 상에 주문형 반도체 소자를 비전도성 접착제를 이용하여 초음파 및 열 압착 공정으로 본딩하였다. LED 광원, 배터리, 전압 및 전류 제어를 위한 콘덴서 및 저항 등은 유연성 플라스틱 기판의 내열성을 고려하여 인체 적합성 에폭시(Ag epoxy)등을 이용하여 본딩하였다.Specifically, after depositing a metal such as gold or aluminum at 200 to 500 nm on a flexible transparent substrate of 30 μm or less, a pad was formed using a wet/dry etching method using a photolithography process. Thereafter, using a flip-chip bonding process, the custom semiconductor device was bonded on the flexible transparent substrate by ultrasonic and thermal compression processes using a non-conductive adhesive. LED light sources, batteries, capacitors for voltage and current control, and resistors were bonded using a human body compatible epoxy (Ag epoxy) in consideration of the heat resistance of the flexible plastic substrate.
각 소자가 접합된 투명기판은 Laser cutter 등으로 소자 부분만 절삭한 후, 인체 적합성 실리콘 엘라스토머(Si elastomer) 등으로 렌즈를 제작하였다. The transparent substrate to which each element was bonded was cut only on the element part with a laser cutter, etc., and then a lens was fabricated with a human body-compatible silicon elastomer or the like.
이후, 안테나 및 RF 전송 처리 기능이 있는 구동보드를 통해 콘택트렌즈를 구동하였다.Thereafter, the contact lens was driven through a driving board having an antenna and an RF transmission processing function.
도 7은 플라스틱 기판에 구성한 주문형 반도체 및 전자소자를 나타낸다. 7 shows a custom semiconductor and electronic device configured on a plastic substrate.
구체적으로, 도 7은 설계 도면(왼쪽 도면) 및 유연성 투명기판 위 플립-칩 본딩, LED 광원 등의 Ag 에폭시 본딩 후의 사진(오른쪽 사진)을 나타낸다. 상기 도 7을 통해, 투명기판 위 패터닝 본딩된 주문형 반도체 소자의 플립-칩 본딩 결과를 확인할 수 있다. 또한 LED 광원, 콘덴서, 배터리, 저항 등의 전자소자를 Ag 에폭시를 이용하여 본딩 후 작동 상태를 확인하였다.Specifically, FIG. 7 shows a design drawing (left view) and a photo (right photo) after flip-chip bonding on a flexible transparent substrate and Ag epoxy bonding of an LED light source. Referring to FIG. 7, a result of flip-chip bonding of the custom semiconductor device patterned-bonded on the transparent substrate can be confirmed. In addition, after bonding electronic devices such as LED light sources, capacitors, batteries, and resistors using Ag epoxy, the operation status was confirmed.
또한, 도 8은 제작된 스마트 포토닉 렌즈 및 구동예를 나타낸다.In addition, FIG. 8 shows a manufactured smart photonic lens and a driving example.
토끼 눈에 히알루론산-로즈벵갈 접합체를 도포 후 LED가 장착된 스마트 콘택트렌즈를 착용하여 손상된 각막 접합, 원추각막 치료 또는 시력교정 등에 적용할 수 있음을 확인할 수 있다. 또한, 열화상 카메라 분석을 통해 LED를 구동하여도 안구내 온도 변화가 1℃ 미만으로 안전성에 문제가 없음을 확인하였다.After applying the hyaluronic acid-rose bengal conjugate to rabbit eyes, it can be confirmed that it can be applied to damaged cornea bonding, conical cornea treatment, or vision correction by wearing a smart contact lens equipped with an LED. In addition, through thermal imaging camera analysis, it was confirmed that there was no problem in safety as the temperature change in the eyeball was less than 1℃ even when the LED was driven.
본 발명에 따른 시스템은 손상된 각막 접합, 원추각막, 각막의 손상 등의 치료에 이용될 수 있으며, 크게는 전 범위적인 시력교정에도 사용될 수 있다.The system according to the present invention can be used to treat damaged cornea junctions, conical corneas, cornea injuries, and the like, and can be used for a wide range of vision correction.

Claims (10)

  1. 히알루론산-염료 접합체; 및 Hyaluronic acid-dye conjugate; And
    LED 광원을 포함하는 콘택트렌즈를 포함하는 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템. Damaged cornea bonding, conical cornea treatment or vision correction system comprising a contact lens including an LED light source.
  2. 제 1 항에 있어서,The method of claim 1,
    히알루론산은 히알루론산(Hyaluronic acid, HA), 히알루론산의 염, 또는 히알루론산의 유도체이며, Hyaluronic acid is hyaluronic acid (HA), a salt of hyaluronic acid, or a derivative of hyaluronic acid,
    상기 히알루론산의 분자량은 10,000내지 3,000,000 달톤(Da)인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.The molecular weight of the hyaluronic acid is 10,000 to 3,000,000 Daltons (Da) damaged cornea conjugation, conical cornea treatment or vision correction system.
  3. 제 1 항에 있어서,The method of claim 1,
    염료는 로즈뱅갈, 리보플라빈, 에틸 에오신, 에오신 Y, 플루오레세인, 2,2-다이메톡시, 2-페닐아세토페논, 2-메톡시, 2-페닐아세토페노노, 캄포르퀴논, 메틸렌 블루, 에리트로신, 플록심, 티오닌 및 메틸렌 그린으로 이루어진 그룹으로부터 선택된 하나 이상인 것인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.Dyes include rosebangal, riboflavin, ethyl eosin, eosin Y, fluorescein, 2,2-dimethoxy, 2-phenylacetophenone, 2-methoxy, 2-phenylacetophenono, camphorquinone, methylene blue, A system for damaged corneal conjugation, conical cornea treatment or vision correction, which is one or more selected from the group consisting of erythrosine, phloxime, thionine, and methylene green.
  4. 제 1 항에 있어서,The method of claim 1,
    히알루론산-염료 접합체는 히알루론산의 카르복실기와 염료의 카르복실기가 링커를 통해 결합된 것인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.The hyaluronic acid-dye conjugate is a damaged corneal conjugation, conical cornea treatment or vision correction system in which the carboxyl group of hyaluronic acid and the carboxyl group of the dye are bonded through a linker.
  5. 제 4 항에 있어서,The method of claim 4,
    링커는 디아민 화합물이며,The linker is a diamine compound,
    상기 디아민 화합물은 디아미노헥세인(헥사메틸렌디아민), 에틸렌디아민, 부틸렌디아민, 펜타에틸렌헥사아민 및 1,5-디아미노-2-메틸펜탄로 이루어진 그룹으로부터 선택된 하나 이상인 것인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.The diamine compound is at least one selected from the group consisting of diaminohexane (hexamethylenediamine), ethylenediamine, butylenediamine, pentaethylenehexaamine and 1,5-diamino-2-methylpentane, damaged corneal conjugation, Conical cornea treatment or vision correction system.
  6. 제 1 항에 있어서,The method of claim 1,
    콘택트렌즈는 실리콘 엘라스토머(Silicone elastomer)의 탄성중합체; 실리콘 하이드로젤(Silicone hydrogel); 폴리디메틸록산(PDMS); 폴리(2-하이드록시에틸메타크릴레이트)(PHEMA); 및 폴리에틸렌 글라이콜메타아크릴레이트(poly(ethylene glycol) methacrylate, PEGMA);로 이루어진 그룹으로부터 선택된 하나 이상을 기반으로 하는 것인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.Contact lenses include silicone elastomer elastomers; Silicone hydrogel; Polydimethyloxane (PDMS); Poly(2-hydroxyethylmethacrylate) (PHEMA); And polyethylene glycol methacrylate (poly(ethylene glycol) methacrylate, PEGMA); damaged corneal junction, conical cornea treatment or vision correction system based on at least one selected from the group consisting of.
  7. 제 1 항에 있어서,The method of claim 1,
    콘택트렌즈는 표면이 평평한 것인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.A contact lens is a system for bonding damaged corneas, conical cornea treatment or vision correction, which has a flat surface.
  8. 제 1 항에 있어서,The method of claim 1,
    LED 광원은 350 내지 550 nm의 파장의 빛을 조사하는 것인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.The LED light source is a damaged corneal junction, conical cornea treatment or vision correction system that irradiates light of a wavelength of 350 to 550 nm.
  9. 제 1 항에 있어서,The method of claim 1,
    손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템은 스마트 안경을 추가로 포함하며, Damaged cornea bonding, conical cornea treatment or vision correction system additionally includes smart glasses,
    상기 스마트 안경에서 송신된 전기적인 신호를 통해 콘택트렌즈가 구동하는 것인 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템.The contact lens is driven through the electrical signal transmitted from the smart glasses, damaged cornea bonding, conical cornea treatment or vision correction system.
  10. 대상의 각막에 히알루론산-염료 접합체를 적용하는 단계;Applying a hyaluronic acid-dye conjugate to the cornea of the subject;
    LED 광원을 포함하는 콘택트렌즈를 착용하는 단계; 및 Wearing a contact lens including an LED light source; And
    콘택트렌즈 내의 LED 광원에서 대상의 각막으로 빛을 조사하는 단계를 포함하는 Including the step of irradiating light from the LED light source in the contact lens to the cornea of the target
    제 1 항에 따른 손상된 각막 접합, 원추각막 치료 또는 시력교정용 시스템을 사용한 손상된 각막 접합, 원추각막 치료 또는 시력교정 방법.Damaged cornea conjugation according to claim 1, conical cornea treatment or damaged cornea conjugation using a system for vision correction, conical cornea treatment or vision correction method.
PCT/KR2020/012280 2019-09-11 2020-09-11 System for corneal cross-linking and correcting vision by using led contact lens and eye dye WO2021049898A1 (en)

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